Three new inbred autoimmune murine strains, MRL/Mp-1pr/1pr, MRL/Mp-+/+, and BXSB, as a group share many immunopathologic features characteristic of human autoimmune disease in general, and systemic lupus erythematosus and rheumatoid arthritis in particular. Study of these new strains has already led to new concepts not apparent from investigation of New Zealand mice alone, but of potential relevance to human autoimmunity. Our discovery of anti-Sm antibody and IgG/anti-IgG complexes in the MRL strains are of special interest in this regard because of the particular association of these elements with systemic lupus erythematosus and rheumatoid vasculitis, respectively. Projects are planned to define further the nature and significance of these antibody specificities in murine and human systems. Particular efforts will be made to characterize oligoclonal anti-Sm antibodies encountered in autoimmunity and in myeloma and to identify common idiotypes. Hybridomas synthesizing large amounts of anti-Sm and other autoantibodies will be developed. Novel approaches have been devised to analyze the constituents of pathogenetic immune complexes, both in the circulation and at sites of tissue injury. Previous investigations of young NZB mice indicate the presence of increased B-cell activation. This phenomenon and the cellular requirements involved will be studied in the context of erythrocyte autoantibody, rheumatoid factor, and antinuclear antibody formation in the autoimmune strains. Anti-idiotypic antibodies, including those arising spontaneously, will be examined with regard to their role in regulation of autoimmune responses. As several of the new autoimmune strains appear to have relatively discrete genetic defects, these will be used as models to provide clues into the more complex hereditary bases of autoimmune disease in man.